Microparticles are particles generally less than 2 millimeters in diameter and are typically spherical. Common microparticles generally comprise a matrix forming material, such as a polymer. A variety of substances can be encapsulated by microparticles. These substances can be released from the microparticle through various mechanisms, including controlled-release mechanisms wherein the substance passes through the microparticle matrix over time and also including rupture-release or degradation mechanisms wherein the microparticle matrix ruptures, degrades, or erodes over time to release the substance.
Several processes exist for preparing microparticles. Emulsion-based processes for making microparticles usually begin with the preparation of two separate phases: a first phase, typically referred to as a dispersed phase, which generally comprises a dispersion or solution of an agent, which is the substance to be encapsulated, in a dispersion or solution of polymer in a first solvent, and a second phase, typically referred to as a continuous phase, which generally comprises a second solvent that is at least partially immiscible with the first solvent of the dispersed phase. After the first and second phases are prepared, they are combined using dynamic or static mixing to form an emulsion, wherein microdroplets of the first phase are dispersed in the continuous phase. The microdroplets then are hardened to form microparticles that contain the agent. The hardening step is carried out by removal of the first solvent from the microdroplets, generally by either an extraction or evaporation process.
The emulsion forming step is often carried out using a mixing device. In one specific example, with reference to FIG. 1A, a mixing device comprises a rotor/stator workhead assembly 1100 having an inlet port 1101 for introducing liquid and solid 1104a materials, which constitute the combined dispersed and continuous phases, into the workhead assembly 1100. Liquid and solid 1104a materials are drawn into the workhead assembly 1100 by powerful suction created by a rotor element 1106 comprising rotor blades that is rotated by a shaft 1102. The rotor blades are positioned substantially perpendicular to a stator element 1107. Materials exit the workhead assembly at exit port 1103.
Referring now to FIG. 1B, as the liquid and solid 1104a materials are drawn into the workhead assembly 1100, centrifugal force created by the rotor element 1106 drives the materials toward the stator element 1107.
Referring now to FIG. 1C, the materials then pass through perforations in the stator element 1107 and are driven toward the periphery of the workhead assembly 1100. The materials are forced through the perforations of the stator element 1107 at a velocity that subjects the materials to intense hydraulic shear. The material then exits the workhead assembly at exit port 1103. The mixing action of the workhead assembly forces the dispersed phase into the continuous phase to form an emulsion comprising microdroplets of the dispersed phase in the continuous phases.
One disadvantage of using a workhead assembly such as the assembly shown in FIGS. 1A-C is that the overall microparticle preparation process can be low-yielding and can result in broad particle size distributions. Accordingly, a need exists for new mixing assemblies and processes using the mixing assemblies that overcome the disadvantages often encountered with typical mixing assemblies used in microparticle production processes. This need and other needs are satisfied by the present invention.